title: Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes.
abstract: OBJECTIVE
  To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM).
  
  
  METHODS
  This was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia with 3-Tesla MRI, and neuropsychological evaluation.
  
  
  RESULTS
  Intranasal insulin administration was well tolerated and did not affect systemic glucose levels. No serious adverse events were reported. Across all subjects, intranasal insulin improved visuospatial memory (P ≤ 0.05). In the DM group, an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group (P = 0.0003). Cognitive performance after insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the DM group (R(2)adjusted = 0.44, P = 0.0098) and in the verbal fluency test in the control group (R(2)adjusted = 0.64, P = 0.0087) were correlated with vasodilatation in the middle cerebral artery territory.
  
  
  CONCLUSIONS
  Intranasal insulin administration appears safe, does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 DM, potentially through vasoreactivity mechanisms. Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions, such as insular cortex that regulates attention-related task performance. Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy.
authors.affiliation: Corresponding author: Vera Novak, vnovak@bidmc.harvard.edu.
authors.forename: Vera
authors.initials: V
authors.lastname: Novak
authors.forename: William
authors.initials: W
authors.lastname: Milberg
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.forename: Medha
authors.initials: M
authors.lastname: Munshi
authors.forename: Peter
authors.initials: P
authors.lastname: Novak
authors.forename: Andrew
authors.initials: A
authors.lastname: Galica
authors.forename: Bradley
authors.initials: B
authors.lastname: Manor
authors.forename: Paula
authors.initials: P
authors.lastname: Roberson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.forename: Amir
authors.initials: A
authors.lastname: Abduljalil
mesh_terms: D000281:Administration, Intranasal; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D018810:Magnetic Resonance Angiography; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin